Solid preparations in the fields of medicine, food, etc., have such problems that preparations composed only of a principal ingredient sometimes cannot exhibit an effect of the ingredient fully because they do not disintegrate sufficiently even when they are administered; and solid preparations in the form of tablets or granules cannot retain their shape because of a poor binding property. In such a case, addition of a disintegrant such as low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium salt, crosslinked carboxymethylcellulose sodium, cross-linked polyvinylpyrrolidone, or carboxymethyl starch can improve the disintegration property. On the other hand, addition of crystalline cellulose or a water-soluble binder can improve the binding property. Low-substituted hydroxypropyl cellulose is known as a unique additive having both the disintegration property and the binding property. In addition to this advantage, the low-substituted hydroxypropyl cellulose is nonionic so that it is free from deterioration due to the reaction with an ionic drug.
Japanese Patent Application Examined Publication Nos. 48-38858/1973 and 57-53100/1982 describe that low-substituted hydroxypropyl cellulose can be used as an additive to pharmaceuticals.
Low-substituted hydroxypropyl cellulose can be prepared by reacting alkali cellulose with propylene oxide as described in Japanese Patent No. 3408398.
Examples of the dosage form in the fields of medicine, food, etc., include tablets, capsules and granules. Of these, the tablets are most popular from the standpoint of convenience and administration ease.
Examples of the method for preparing a tablet may include a dry direct tableting method in which after dry mixing of a drug with a binder, a disintegrant, an extender, a lubricant, and the like, the resulting mixture is tableted; and a wet granulation tableting method in which after a drug, a binder, a disintegrant, an extender, and the like are granulated using water or an aqueous solution of a binder and the resulting granule is dried, powders thus obtained and a lubricant are mixed, followed by tableting.
In the wet granulation tableting method, it is the common practice to place a drug, a binder, a disintegrant, an extender and the like in powder form in a fluidized bed granulator or high speed agitation granulator, and granulate the mixture by using water, ethanol or the like. It is, however, known that when tablets having predetermined tablet hardness cannot be obtained or tableting problems such as capping, lamination and sticking occur, granulating while spraying or adding an aqueous solution of a water-soluble binder such as hydroxypropyl cellulose, polyvinylpyrrolidone, or hydroxypropylmethyl cellulose is effective for achieving high tablet hardness. However, the tablet obtained in such a manner has undesirably a reduced disintegration property because of the use of a water-soluble binder.
In recent years, there has been a demand for the development of rapidly disintegrating oral tablets which elderly or infant patients having an insufficient ability to swallow can easily take without water. Preparation technologies of such tablets are described in the following known literatures.
Japanese Patent Application Unexamined Publication No. 9-48726/1997 discloses a method of forming a drug into a tablet under a humidified condition and then drying it. As a base material for them, sugar, sugar alcohol and water-soluble polymer are exemplified. Japanese Patent Application Unexamined Publication No. 5-271054/1993 discloses a method for preparing a rapidly disintegrating oral tablet containing a drug component and sugar. However, these technologies have such problems that they are very cumbersome, they require special equipment, and tablets thus obtained are likely to cause wear losses or cracks during shipping because they are low in strength.
The following are known literatures on rapidly disintegrating oral tablets using low-substituted cellulose ether.
Japanese Patent Application Unexamined Publication No. 9-71532/1997 discloses rapidly disintegrating oral tablets containing microcrystalline cellulose and low-substituted hydroxypropyl cellulose at a certain ratio. This invention relates to a mixture of low substituted hydroxypropyl cellulose and microcrystalline cellulose, but it requires addition of large amounts of additives and the tablets thus obtained do not have a satisfactory disintegration property.
Japanese Patent Application Unexamined Publication No. 11-43429/1999 describes use of low-substituted hydroxypropyl cellulose having a degree of hydroxypropoxyl group substitution ranging from 7.0 to 9.9% by weight for preparing rapidly disintegrating oral tablets. Similarly, Japanese Patent Application Unexamined Publication No. 2000-103731 describes use of low-substituted hydroxypropyl cellulose having a degree of hydroxypropoxyl group substitution ranging from 5.0 to 7.0% by weight for the same purpose. Since a fibrous condition derived from raw material pulp becomes severer with a decrease in the degree of hydroxypropoxyl group substitution, when the tablets thus obtained disintegrate in the oral cavity, they leave an unpleasant texture to recipients as if they eat paper.
Japanese Patent Application Unexamined Publication No. 2001-328948 describes rapidly disintegrating oral tablets composed of low-substituted hydroxypropyl cellulose and sugar alcohol. However, the method disclosed herein does not succeed in providing a tablet having high tablet hardness.
Japanese Patent Application Unexamined Publication No. 2002-104956 describes a base material for dry direct tableting obtained by impregnating low-substituted hydroxypropyl cellulose with sugar or sugar alcohol and then drying the resulting mixture. It is not obtained by granulating using an aqueous dispersion of low-substituted hydroxypropyl cellulose.
Japanese Patent Application Unexamined Publication No. 2002-308760 describes sugar coated with aluminometasilicate. However, it is not obtained by granulating using an aqueous dispersion of low-substituted hydroxypropyl cellulose.
Japanese Patent Application Unexamined Publication No. 2006-282551 describes use of α-starch or the like as a binder soluble or swellable in water, together with delta type mannitol. However, it does not include description of low-substituted hydroxypropyl cellulose.